螺内酯对老年人轻度心力衰竭心肌纤维化和心功能的影响

目的:探讨螺内酯对老年人轻度心力衰竭心肌纤维化和心功能的影响。方法:选择老年轻度心力衰竭患者(NYHA心功能分级为Ⅰ～Ⅱ级)67例为观察组,再随机分为常规治疗组(33例)和螺内酯组(34例);另健康对照组20例,治疗前和治疗3个月时采用放射免疫法测定血清Ⅲ型前胶原氨基半端肽(PⅢNP)和血浆脑钠肽(BNP)浓度,并应用心脏彩超测定心功能变化。结果:观察组血清PⅢNP和血浆BNP浓度均高于对照组(P<0.01);3个月后与治疗前比较:螺内酯组血PⅢNP和BNP均明显下降(P<0.01);且较常规治疗组亦明显下降(P<0.05,<0.01)。结论:在老年人轻度心力衰竭患者小剂量螺内酯治疗可以起到抗心肌纤维化、改善心功能的作用。     

缬沙坦和螺内酯抑制自发性高血压大鼠心肌纤维化的对比研究

目的比较缬沙坦和螺内酯对自发性高血压大鼠(SHR)心肌纤维化的抑制作用及二者对SHR心肌整合素β1和纤维黏连蛋白(FN)表达的影响,探讨SHR心肌纤维化的机制。方法将18只6周龄SHR随机均分成3组缬沙坦组(缬沙坦30mg·kg-1·d-1),螺内酯组(螺内酯20mg·kg-1·d-1)和SHR组,并与雄性同周龄WKY6组只比较,实验期14周。比较血压、左室重量/体重(LVM/BW)、胶原容积分数(CVF)和血管周围胶原面积(PVCA),并用免疫组化法检测4组大鼠心肌整合素β1和FN的表达。结果(1)缬沙坦组和螺内酯组血压〔(1125±88)mmHg和(1316±51)mmHg〕、LVM/BW〔(284±014)×10-3和(322±015)×10-3〕、CVF〔(321±022)%和(400±028)%〕、PVCA〔(062±015)%和(094±056)%〕均显著低于SHR组(P<005),缬沙坦组与螺内酯组比较,差异有显著性(P<005);(2)SHR组心肌整合素β1和FN的表达明显高于WKY组〔其积分吸光度值(A)分别为(15687±2033)、(5430±800)和(45665±4127)、(15718±2830),P<001,而缬沙坦组和螺内酯组FN的沉积较SHR组(45665±4127)均显著减少〔分别为(20047±1680)和(21358±800),P<005〕;缬沙坦组整合素β1的表达(9892±135)较SHR组下降(P<005),而螺内酯组整合素β1的表达与SHR组差异无显著性(P>005)。结论缬沙坦和螺内酯不仅可以良好控     

螺内酯对原发性高血压大鼠左心室功能的影响

目的用超声评价螺内酯对原发性高血压(高血压)大鼠(SHR)心肌组织胶原含量和心功能的影响。方法20只雄性高血压大鼠随机分为螺内酯组(n=10)和安慰剂组(n=10),另设WKY组(n=7)。螺内酯组螺内酯用双蒸水溶解后以20 mg.kg-1.d-1灌胃;安慰剂组和WKY组用等容积双蒸水灌胃,连续16周。超声心动图观察大鼠左心房内径,室间隔和后壁厚度,射血分数,背向散射积分(IBS);背向散射积分周期变化(PPI)。取心肌标本,称取左心室重量,计算左心室质量指数,制备心肌组织石蜡切片,天狼猩红饱和苦味酸染色,观察心肌胶原容积分数(CVF)和血管周围胶原面积(PVCA)。结果与WKY组比较,安慰剂组大鼠心肌肥厚指标:左心室质量指数室,室间隔及左心室后壁厚度增加;心脏功能指标:左心房内径、射血分数增大,E/A比值减少;纤维化指标:胶原容积分数、血管周围胶原面积增加,声学密度指标背向散射积分升高,背向散射积分周期变化降低,差异有统计学意义(P<0.05)。治疗16周,与安慰剂组比较,螺内酯组上述指标均有改善,差异有统计学意义(P<0.05)。结论高血压大鼠左心室胶原沉积、心肌肥厚、舒张功能减退,收缩功能受损。螺内酯治疗能减少高血压大鼠局部胶原沉积,改善左心室功能。     

小剂量贝那普利联合螺内酯对自发性高血压大鼠心肌纤维化的干预作用及超声背向散射积分评价

目的观察小剂量贝那普利联合螺内酯对自发性高血压大鼠(SHR)左室心肌纤维化的影响,并应用超声背向散射积分(IBS)进行评价。方法21只雄性SHR随机分成模型对照组(SHR组)、贝那普利干预组[SHR-B组,贝那普利10mg/(kg·d)灌胃]及小剂量贝那普利联合螺内酯干预组[SHR-BS组,贝那普利5mg/(kg.d)+螺内酯10mg/(kg·d)灌胃],另外选择同周龄雄性Wistar大鼠设为正常对照组(WKY组),SHR组及WKY组蒸馏水灌胃2mL/d。12周后超声测量IBS参数[峰-峰强度(PPI);平均图像强度(AII)];对心肌组织进行羟脯氨酸含量(HPC)测定,Masson染色计算胶原容积分数(CVF)、血管周围胶原面积(PVCA)、冠状小动脉管壁厚/管外径比值(T/D),嗜银染色计算嗜银纤维容积分数(APFVF),对结缔组织生长因子(CTGF)蛋白表达的半定量分析进行免疫组织化学染色。结果与WKY组比较,SHR组的超声AII%明显增高,PPI减低,SHR组的纤维化指标(HPC、CVF、PVCA、T/D、APFVF、CTGF的表达)增高。干预后,与SHR组比较AII%减低,PPI增高,纤维化指标减轻...     

螺内酯防治实验性大鼠肝纤维化作用研究

探讨螺内酯对肝纤维化的防治作用。雄性SD大鼠46只,随机分成对照组(6只);模型组(30只),复合因素制成肝纤维化模型;螺内酯预防组(10只),造模方法同模型组,螺内酯每天100mg·11ml灌胃。于第8W末,将模型组(16只)再随机分为A组(肝硬化组)8只,用等量自来水灌胃;B组(螺内酯治疗组)8只,螺内酯灌胃8w。分别观察肝内纤维组织变化。显示螺内酯预防组肝脏I、Ⅲ型胶原、纤维连接蛋白、层粘蛋白增生明显减低(PO.05)。     

螺内酯预防L-硝基精氨酸诱导持续性高血压大鼠心肌重塑

目的：探讨醛固酮受体拮抗剂螺内酯（ｓｐｉｒｏｎｏｌａｃｔｏｎｅ，安体舒通）预防一氧化氮减少致高血压心肌重塑的可行性。方法：取８周龄雄性Ｗｉｓｔａｒ大鼠１９只，随机分成高血压大鼠实验组１２只，其中又分为高血压组、预防组各６只；正常血压对照组７只。高血压大鼠实验组用Ｌ－硝基精氨酸（Ｎ－ｏｍｅｇａ－ｎｉｔｒｏ－Ｌ－ａｒｇｉｎｉｎｅ，ＬＮＮＡ，７．５ｍｇ／ｋｇ，腹腔注射，每日２次，共４周）诱导高血压心肌重塑大鼠１２只，其中６只同时以安体舒通（２０ｍｇ／ｋｇ，每日１次，灌胃，共４周）治疗。分别观察其动脉血压、左心室相对重量、丝裂素活化蛋白激酶（ｍｉｔｏｇｅｎ－ａｃｔｉｖａｔｅｄｐｒｏｔｅｉｎｋｉｎａｓｅ，ＭＡＰＫ）活性、胶原蛋白含量、亚硝酸盐浓度、心肌组织形态学改变等。结果：高血压组亚硝酸盐浓度降低，血压、ＭＡＰＫ活性及胶原蛋白含量均明显升高，左心室肥大，心肌细胞肥大及心肌纤维化。安体舒通可明显降低动脉压、ＭＡＰＫ活性，减轻左心室肥大、心肌细胞肥大及心肌纤维化。结论：安体舒通通过竞争性抑制醛固酮与其受体结合，降低ＭＡＰＫ活性，可防止一氧化氮生成减少所致高血压心肌重塑及血压持续升高。     

缬沙坦和螺内酯对自发性高血压大鼠心肌整和素β1的作用

目的　比较自发性高血压大鼠 (SHR)和WKY心肌整和素β1的表达以及缬沙坦和螺内酯对SHR整和素 β1的影响。方法　将 18只 6周龄SHR随机分成 3组 ,每组 6只。其中 2组分别灌喂缬沙坦 2 0mg·kg- 1·d- 1,和螺内酯 10mg·kg- 1·d- 1,另一对照组给正常饮水 ,并与雄性同周龄WKY6只比较。实验期 14周 ,免疫组化法检测四组大鼠心肌整和素 β1的表达。结果　SHR对照组心肌整和素 β1表达明显高于WKY组 ,和SHR对照组比较缬沙坦组整和素 β1的表达下降 (P <0 0 5) ,而螺内酯组整和素 β1的表达无显著改变 ;两治疗组血压、LVM/BW以及心肌纤维化程度均显著低于SHR组 (P <0 0 5) ,而且两治疗组间比较缬沙坦组血压和心肌纤维化程度降低更明显 (P <0 0 5)。结论　缬沙坦除降低血压外 ,还能抑制整和素 β1表达 ,而螺内酯对整和素β1的表达无明显抑制作用 ;而缬沙坦对心肌纤维化的抑制作用优于螺内酯。提示整和素 β1在高血压心肌纤维化进程中起了一定作用     

螺内酯抗CaN依赖的肾性高血压大鼠心肌肥大的研究

目的观察螺内酯(Spironolactone,Spiro)抗钙调神经磷酸酶(calcineurin,CaN)依赖的肾性高血压大鼠心肌肥大的作用.方法20只Wistar大鼠随机分为3组两组采用一肾一夹模型制造肾性高血压,其中spiro组(n=7)给予螺内酯灌胃,op组(n=7)予水灌胃;假手术组(sham op n=6)只给予水灌胃.称重法测定心重比,发色底物法测CaN活性;同时用免疫组织化学染色方法,观察心肌中CaN及活化T细胞核因子(nuclear factor of activatedT cell,NFAT)的表达.结果肾性高血压大鼠经螺内酯灌胃4周,其心重比较未干预组明显降低(P＜0.05),心肌肥大受到抑制,同时发现心肌中CaN活性较未干预组显著下降,免疫组化显示螺内酯干预组心肌中CaN及NFAT表达降低.结论螺内酯抑制肾性高血压心肌肥大的机制与其下调心肌胞浆中CaN表达及其活性有关.     

螺内酯通过上调沉默信息调节因子1减轻异丙肾上腺素诱导大鼠心肌纤维化

目的探讨螺内酯减轻大鼠心肌纤维化是否与沉默信息调节因子1(SIRT1)的表达变化有关。方法雄性SD大鼠40只,随机均分为对照组、模型组、低剂量螺内酯组、高剂量螺内酯组。后3组皮下注射异丙肾上腺素[5 mg/(kg·d),连续7天]建立大鼠心肌纤维化模型,低剂量螺内酯组、高剂量螺内酯组大鼠在给予异丙肾上腺素的同时分别给予30、60 mg/(kg·d)螺内酯灌胃,对照组给予相同体积的生理盐水,共21天。Powerlab生理记录仪检测左心功能变化,HE染色和Masson染色检测心肌病理改变,Western blot和实时荧光定量PCR检测大鼠心肌组织SIRT1的表达变化。结果模型组大鼠的左心室质量指数(LVWI)、右心室质量指数和左心室舒张末期压(LVEDP)显著高于对照组(P0.05);模型组左心室收缩压(LVSP)、左心室压力上升的最大变化速率(+dp/dt_(max))和左心室压力下降的最大变化速率(-dp/dt_(max))显著低于对照组(P0.05);与对照组比较,模型组大鼠心肌排列紊乱,胶原纤维增生明显,SIRT1的mRNA及蛋白表达下调(P0.05)。给予螺内酯后,大鼠的LVWI和LVEDP明显低于模型组(P0.05),LVSP、+d P/dt_(max)和-dp/dt_(max)明显高于模型组(P0.05);与模型组相比,螺内酯组大鼠心肌排列紊乱程度减弱,胶原含量减少,SIRT1的mRNA及蛋白表达上调(P0.05)。结论螺内酯减轻异丙肾上腺素诱导大鼠的心肌纤维化,其抗纤维化作用可能与上调SIRT1表达有关。     

Quantitation of myocardial fibrosis and its relation to function in essential hypertension and hypertrophic cardiomyopathy

Myocardial interstitial fibrosis is an important microscopic feature of hypertrophic cardiomyopathy. To determine whether interstitial fibrosis of the myocardium in hypertrophic cardiomyopathy and essential hypertension differ in quality or quantity, and to determine whether fibrosis affects cardiac function directly, we measured the percentage of fibrosis in patients of both categories and compared the severity of fibrosis with several cardiac functions. Left and right ventricular endomyocardial biopsies were performed in 25 patients with essential hypertension and in 19 patients with hypertrophic cardiomyopathy. Interstitial fibrosis was classified into four different microscopic types, and the percentage of total and of each type was calculated using the point-counting method. Although the percentage of total fibrosis was similar between the two groups, the type of fibrosis was different. There was no correlation between the percentage of total fibrosis and the mean size of myocytes in either group. Although there was a significant correlation between the percentage of total fibrosis and the thickness of the interventricular septum in hypertrophic cardiomyopathy, such correlation was lacking in hypertension. There was no correlation between the percentage of total fibrosis and the ejection fraction, cardiac index, or left ventricular end-diastolic pressure in either group. We concluded that the amount of myocardial interstitial fibrosis in hypertrophic cardiomyopathy is no greater than that in essential hypertension, but the type of fibrosis is different. Furthermore, in subjects in whom the ejection fraction is normal or only slightly decreased, fibrosis does not influence global cardiac functions.     

Effects of simvastatin, pentoxifylline and spironolactone on hepatic fibrosis and portal hypertension in rats with bile duct ligation

Aims/Methods: Our aim was to the antifibrotic and hemodynamic effects of simvastatin (SMV), pentoxifylline (PTX) and spironolactone (SPN), three drugs which may have antifibrotic and/or portal hypotensive properties, in a model of hepatic fibrosis and portal hypertension induced in rats by bile duct ligation. A blind study was performed in five groups of 53 Sprague-Dawley rats: sham, placebo (PL), SMV (2.5 mg·kg⁻¹·J⁻¹, PTX (50 mg·kg⁻¹·J⁻¹) and SPN (100 mg·kg⁻¹·J⁻¹). Drugs were administered by daily gavage over a 4-week period as soon as bile duct ligation was performed. At day 28, the following parameters were evaluated: area of hepatic fibrosis by image analysis after staining collagen with picrosirius and plasma concentrations of hyaluronate, splanchnic and systemic hemodynamics (radiolabeled microspheres).Results: Portal venous pressure (PL: 15.5±1.5, SMV: 15.8±2.5, PTX: 15.9±1.8, SPN: 13.5±2.1 mmHg, p<0.05) and porto-systemic shunts (PL: 30±31, SMV: 18±27, PTX: 25±24, SPN: 5±4%, p<0.05) were significantly reduced in the SPN group; other hemodynamic parameters were not significantly altered. There was a significant correlation between porto-systemic shunts and portal pressure (r_s=0.47, p<0.01). The area of fibrosis was not significantly different among the four groups of bile duct ligated rats (PL: 8.7±3.9, SMV: 7.1±3.6, PTX: 7.8±2.7, SPN: 6.6±3.3%) but was higher than in sham rats (1.5±0.5%, p<0.001). Hyaluronate was significantly higher in bile duct ligated rats (from 374±162 to 420±131 μg/l, among the four groups) than in sham rats (52±16 μg/l, p<0.0001).Conclusions: In this model, none of the drugs prevented hepatic fibrosis. On the other hand, spironolactone decreased portal pressure and prevented porto-systemic shunts. Therefore, this drug may have beneficial effect in patients with early portal hypertension.     

The effect of spironolactone, cilazapril and their combination on albuminuria in patients with hypertension and diabetic nephropathy is independent of blood pressure reduction: a randomized controlled study.

OBJECTIVE: The effect of spironolactone, cilazapril and their combination on albuminuria was examined in a randomized prospective study in female patients with diabetes and hypertension. PATIENTS AND METHODS: Sixty female diabetic patients aged 45-70 years with blood pressure (BP) 140-180/90-110 mmHg, serum creatinine (sCr) < or = 160 micro mol/l, HbA(1c) < or = 10%, and albuminuria were treated by atenolol 12.5-75 mg/d and hydrochlorothiazide 6.25-25 mg/d. Titration-to-target helped to reach BP values < or = 135/85 mmHg in 46 patients after 12 weeks. These patients were randomized to spironolactone 100 mg/d or cilazapril 5 mg/d for 24 weeks. Then both groups received spironolactone 50 mg/d and cilazapril 2.5 mg/d for 24 weeks. BP was stabilized by tapering the dose of the initial agents. Urinary albumin/creatinine ratio (ACR), BP, K(+). sCr and HbA(1c) were assessed at baseline and at weeks 12, 16, 36 and 60. RESULTS: The average BP at week 12 was 128 +/- 4/81 +/- 3 mmHg and remained constant, in both groups, throughout the study. ACR declined on spironolactone from a median value (range) of 452 (124-1571) to 216 (64-875) mg/g (P = 0.001), and on cilazapril to 302 (90-975) mg/g (P = 0.001). The difference between spironolactone and cilazapril was significant (P = 0.002). Combined treatment resulted in a further modest decline in ACR. Serum creatinine was unaltered by spironolactone and rose slightly (121 to 126 micro mol/l, P = 0.02) on cilazapril. CONCLUSION: At the doses tested, spironolactone was superior to cilazapril in reducing albuminuria. Combined administration was more effective than either drug alone. These effects were independent of BP values. Hyperkalaemia was the main side-effect.     

结缔组织生长因子在慢性心力衰竭大鼠心肌纤维化中的表达

目的研究结缔组织生长因子(CTGF)的表达与慢性心力衰竭(CHF)大鼠心肌纤维化的关系。方法选择Wistar雄性大鼠45只,随机取8只为假手术组,其余37只大鼠采用肾上腹主动脉缩窄法制作CHF模型,4周后随机取10只大鼠测血流动力学证实造模成功,存活的24只大鼠随机分为CHF 1 d组,CHF 7 d组,CHF 14 d组,每组8只。各组测心肌胶原容积分数(CVF)及左心室重量指数(LVMI),用HE和Masson染色法观察左心室心肌组织形态的改变。用RT-PCR和Western blot法检测CTGF mRNA及蛋白表达水平。结果与假手术组比较,CHF 1 d组、CHF 7 d组和CHF 14 d组CVF和LVMI明显升高(P<0.01),与CHF 1 d组比较,CHF 7 d组和CHF 14 d组CVF和LVMI升高更明显(P<0.01),且CHF 14 d组较CHF7d组升高更显著(P<0.05)。CHF1d组、CHF 7 d组和CHF 14 d组CTGF mRNA及蛋白表达均明显高于假手术组(P<0.01),各CHF组CTGFmRNA及蛋白表达比较,差异有统计学意义(P<0.05,P<0.01)。结论 CTGF可能参与大鼠压力负荷性心肌肥厚的发生和发展,且与CHF的严重程度密切相关。     

声学密度技术对老年人高血压左房心肌纤维化的临床评价

目的探讨声学密度计最（acoustic densitometry，AD）技术对评价老年人高血压左房心肌纤维化程度的临床应用价值。方法老年高血压病患者54例分为高血压Ⅰ型前胶原羧基端前肽（PICP）〈127μg/L组和高血压PICP〉127μg/L组，健康对照20例。AD技术分别测定左房后壁、左房腔及心包的时间平均图像强度（AII）与心动周期变化幅度（PPI）。放免法测定血清PICP。结果与对照组相比，高血压组AII值明显升高；高血压PICP〉127μg/L组AII值明显高于PICP〈127μg／L组。各组间PPI值变化呈相反趋势。左房后壁AII，经心包及经心腔标比的左房后壁AII均与PICP呈正相关关系．与PCIII无直线相关关系。结论AD技术是检测老年人高血压定房心肌纤维化程度敏感而可行的方法．     

Effect of spironolactone on patients with resistant hypertension and obstructive sleep apnea

Objective: To examine whether spironolactone could reduce the severity of obstructive sleep apnea (OSA) and lower blood pressure in patients with resistant hypertension. Methods: This was a blank-controlled, single-center study. Patients with resistant hypertension and moderate-to-severe OSA (apnea–hypopnea index >15 events/h) were enrolled and randomly assigned to the therapy or control group. Patients in the therapy group were administered spironolactone 20 mg once daily (up to 40 mg once daily for 4 weeks, if required) in addition to original antihypertensive medication. Follow-up was 12 weeks. Results: Thirty patients were enrolled (n = 15 per group). After 12 weeks of follow-up, apnea–hypopnea index (21.8 ± 15.7 vs. 1.8 ± 12.8, p < 0.05), hypopnea index (9.8 ± 11.1 vs. ?2.7 ± 16.8, p < 0.05), oxygen desaturation index (20.8 ± 15.0 vs. 0.3 ± 16.1, p < 0.05), clinical blood pressure, ambulatory blood pressure, and plasma aldosterone level (9.8 ± 6.3 vs. 2.9 ± 6.7, p < 0.05) were reduced significantly in the therapy group compared with the control group. No side effects were reported. Conclusions: Spironolactone reduced the severity of OSA and reduced blood pressure in resistant hypertension patients with moderate-to-severe OSA. These findings may assist in the treatment of OSA in patients with resistant hypertension.     

血管紧张素转换酶基因多态性与原发性高血压病心肌纤维化的关系

目的　探讨血管紧张素转换酶 ( ACE)基因多态性与原发性高血压病 ( EH)心肌纤维化的关系。方法　以多聚酶链反应 ( PCR)方法检测 168例 EH患者的 ACE基因型 ;放射免疫法检测血清 型前胶原 ( PC )、透明质酸( HA)和层粘蛋白 ( LN)。结果　高血压病心肌纤维化组 DD基因型和 D等位基因频率分别为 0 .42 9和 0 .60 ,显著高于非纤维化组 0 .18和 0 .42 1( P<0 .0 5 )。DD型与 II型比较心肌质量指数、PC 显著升高 ,差异有显著性 ( P<0 .0 5 )。结论　 ACE基因 DD型可能是高血压病心肌纤维化的重要危险因素     

软肝煎对非酒精性脂肪肝大鼠肝纤维化的预防作用

目的：观察软肝煎对非酒精性脂肪肝大鼠肝纤维化的预防作用，并探讨其作用机制。方法：将38只SD大鼠随机分为4组，除正常组（N）外，其余3组即模型组（M）、软肝煎低剂量组（L）、软肝煎高剂量组（H）大鼠用高脂饲料喂养共16周，制备大鼠非酒精性脂肪肝模型。L组、H组大鼠以软肝煎低、高剂量灌胃，1次/d，共12周；N、M组大鼠以等量生理盐水灌胃。观察各组大鼠肝组织病理变化及TGF—β1阳性表达情况，检测血清PCⅢ、CⅣ、HA、LN水平，并进行比较。结果：M组大鼠肝组织呈脂肪变、炎性细胞浸润、肝细胞坏死、纤维组织明显增生，L、H组大鼠肝组织病理表现较M组明显减轻；M组大鼠TGF—β1阳性表达较N组增高（P〈0．05），而H组较M组则降低（P〈0.05）；M组大鼠各项血清学指标较N组明显升高（P〈0．05），而L、H组较M则明显降低（均P〈0．05），且此4项指标与肝纤维化存在正相关。结论：软肝煎不仅可以治疗脂肪肝、高脂血症，而且还具有确切地预防非酒精性脂肪肝纤维化作用。     

心肌内膜纤维化与缩窄性心包炎的心电图比较研究

比较17例心肌内膜纤维化(EMF)和82例缩窄性心包炎(CP)患者的心电图表现,结果发现EMF 患者心房扑动或颤动、右心房肥大、左心房肥大和右束支传导阻滞的发生率较 CP 患者高(分别为41%与4%,P<0.01;24%与5%,P<0.05;18%与2%,P<0.05和18%与1%,P<0.05)。而窦性心动过速的发生率则 CP 患者较 EMF 患者高(60%比12%,P<0.01)。低电压、ST 段下移、T 波低平或倒置和房性或室性早搏的发生率两者无显著性差异。